A 38-year-old woman from Delhi presents with a 2-month history of severe fatigue, dyspnea on exertion, and glossitis. On examination, she is pale, has a beefy red tongue, and mild jaundice. Laboratory findings: Hemoglobin 7.2 g/dL, MCV 105 fL, reticulocyte count 0.8%, serum B12 level 150 pg/mL (normal >200), serum folate 1.2 ng/mL (normal >5.4). Peripheral blood smear shows hypersegmented neutrophils. She is a strict vegetarian with no history of pernicious anemia or GI surgery. What is the primary cause of her anemia?

Explanation

## Clinical Diagnosis: Cobalamin (B12) Deficiency from Dietary Insufficiency ### Case Analysis This patient presents with megaloblastic anemia (MCV 105 fL, hypersegmented neutrophils) with **low B12 (150 pg/mL; normal >200)** and **low folate (1.2 ng/mL; normal >5.4)**. She is a **strict vegetarian** with no history of pernicious anemia, GI surgery, or malabsorption. The primary cause is **dietary B12 deficiency**. ### Why B12 Deficiency is Primary in a Strict Vegetarian **Key Point:** Strict vegetarians (especially vegans) are at high risk for B12 deficiency because: 1. **B12 is found exclusively in animal products** (meat, fish, eggs, dairy). A strict vegetarian who avoids all animal products has virtually zero dietary B12 intake. 2. **Folate is abundant in plant foods** (leafy greens, legumes, lentils, chickpeas) — a vegetarian diet is typically folate-rich, not folate-poor. 3. **B12 stores** last 3–5 years, so deficiency develops insidiously — consistent with a 2-month symptomatic history after years of depletion. 4. The **low folate** in this patient is likely secondary: B12 deficiency impairs the methionine synthase reaction, trapping folate as methyltetrahydrofolate ("folate trap"), causing functional folate deficiency even when dietary folate intake is adequate. **High-Yield (Harrison's / KD Tripathi):** In Indian vegetarians, **dietary B12 deficiency is the most common cause of megaloblastic anemia**. The "folate trap" mechanism explains why B12-deficient patients often have low serum folate — it is a consequence, not the primary cause. ### Biochemical Mechanism | Vitamin | Dietary Source | Deficiency in Vegetarians | |---------|---------------|--------------------------| | **B12 (Cobalamin)** | Animal products only | **Primary** — no dietary source | | **Folate (B9)** | Leafy greens, legumes | Secondary (folate trap) or mild co-deficiency | **Clinical Pearl:** B12 deficiency causes the "folate trap" — methyltetrahydrofolate accumulates and cannot be converted to active folate forms, leading to low serum folate. This is why both B12 and folate may appear low in primary B12 deficiency (Harrison's Principles of Internal Medicine, 21st ed.). ### Why Other Options Are Incorrect | Option | Why Wrong | |--------|-----------| | **A: Combined B12 + folate with B12 predominance** | While both are low, the primary etiology is dietary B12 deficiency; the low folate is secondary to the folate trap — not an independent combined deficiency | | **B: Folate deficiency from inadequate dietary intake** | Vegetarian diets are rich in folate; dietary folate deficiency is unlikely in a vegetarian. The low folate is secondary to B12 deficiency (folate trap) | | **C: Intrinsic factor deficiency (pernicious anemia)** | Explicitly excluded by history — no autoimmune disease, no GI surgery, no neurological signs of severe B12 depletion; this is dietary insufficiency | ### Why Not Pernicious Anemia? Pernicious anemia requires autoimmune destruction of gastric parietal cells → intrinsic factor deficiency → B12 malabsorption. This patient has **no GI pathology, no autoimmune history**, and is a strict vegetarian — the mechanism is purely dietary. ### Management - **B12 supplementation**: 1000 μg IM monthly (or oral 2000 μg/day for dietary deficiency) - **Folate supplementation**: 5 mg/day (to replete secondary folate deficiency) - **Dietary counseling**: Fortified cereals, nutritional yeast, dairy (if lacto-vegetarian) **Reference:** Harrison's Principles of Internal Medicine, 21st ed.; KD Tripathi Essentials of Medical Pharmacology, 8th ed.